tbuckley/cabot-search huggingface dataset:
The Gut Microbiome in Melanoma: A Piece of a Complex Puzzle
Authors: Amrit K. Greene, Amanda M. Nelson
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open‐label study
Authors: Lijuan Deng, Zhiming Li, Huilai Zhang, Haiwen Huang, Jianda Hu, Lihong Liu, Ting Liu, Jie Jin, Zunmin Zhu, Wenyu Li, Zhenqian Huang, Wenrong Huang, Keshu Zhou, Haiyan Yang, Mingzhi Zhang, Kaiyang Ding, Hui Zhou, Yu Hu, Yuerong Shuang, Junning Cao, Sujun Gao, Dengju Li, Zimin Sun, Qingyuan Zhang, Shuhua Yi, Chunyan Ji, Liansheng Zhang, Cheng Hou, Yue Du, Weige Wang, Renbin Zhao, Yuqin Song, Jun Zhu
Journal: American Journal of Hematology (2023)

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL.
Erroneous Rapid Exchange Balloon Inflation During Coronary Angioplasty in a Male Patient in His 70s With Chronic Stable Angina
Authors: Shishir K. Roul, Avinash Arke, Saurabh Ajit Deshpande
Journal: JAMA Cardiology (2023)

This case report discusses an erroneous rapid exchange balloon inflation during coronary angioplasty in a patient who presented with a right coronary artery lesion on angiography.
Moral psychology biases toward individual, not systemic, representations
Authors: Irein A Thomas, Nick R Kay, Kristin Laurin
Journal: Behavioral and Brain Sciences (2023)

Abstract We expand Chater &amp; Loewenstein's discussion of barriers to s-frames by highlighting moral psychological mechanisms. Systemic aspects of moralized social issues can be neglected because of (a) the individualistic frame through which we perceive moral transgressions; (b) the desire to punish elicited by moral emotions; and (c) the motivation to attribute agency and moral responsibility to transgressors.
Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers
Authors: Thuy-Dung Nguyen, Kaarina Kowalec, Joëlle Pasman, Henrik Larsson, Paul Lichtenstein, Christina Dalman, Patrick F. Sullivan, Ralf Kuja-Halkola, Yi Lu
Journal: American Journal of Psychiatry (2023)

Objective: Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder's symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity. Methods: Using Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups. Results: Estimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%–58.3%) than the overall MDD sample (45.3%, 95% CI=43.0–47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%–34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data. Conclusions: The findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.
Unpacking the nudge muddle
Authors: Joseph Heath
Journal: Behavioral and Brain Sciences (2023)

Abstract Libertarian paternalism initially focused on policy domains in which the state was prohibited from interfering coercively in decision making out of respect for individual autonomy. Because adjustment of the s-frame was not an option, achieving better outcomes through manipulation of the i-frame seemed attractive. This original motivation was unfortunately lost in the transition from libertarian paternalism to the nudge framework.
Moving from i-frame to s-frame focus in equity, diversity, and inclusion research, practice, and policy
Authors: Joyce C. He, Sonia K. Kang
Journal: Behavioral and Brain Sciences (2023)

Abstract Meaningful and long-lasting progress in equity, diversity, and inclusion (EDI) continue to elude academics, practitioners, and policymakers. Extending Chater &amp; Loewenstein's arguments to the EDI space, we argue that, despite conventional focus on individual-level solutions (i-frame), increasing EDI also requires a systemic focus (s-frame). We thus call for the design, testing, and implementation of multipronged s-frame interventions.
Behavioral public policy in practice: Misconceptions and opportunities
Authors: Michael Hallsworth
Journal: Behavioral and Brain Sciences (2023)

Abstract I greatly respect the authors of the target article. However, in contrast to the target article's assertion, practitioners of behavioral public policy are indeed involved in developing and promoting systemic solutions. Its “i-frame”/“s-frame” distinction is incoherent, unhelpful, and obscures promising future directions for behavioral public policy. Its content and presentation undermine its stated goals and encourage sweeping dismissals of the field.
Nudges, regulations, and behavioral public choice
Authors: Samuel G. B. Johnson, Jason Dana
Journal: Behavioral and Brain Sciences (2023)

Abstract Chater &amp; Loewenstein have done a service to the field by raising the fundamental issue of how the political process distorts well-intentioned efforts at behavioral public policy. We connect this argument to broader research on government failure, particularly public choice theory in economics. We further suggest ways that behavioral research can help identify and mitigate such failures.
Use behavioral research to improve the feasibility and effectiveness of system-level policy
Authors: Todd L Cherry, Steffen Kallbekken
Journal: Behavioral and Brain Sciences (2023)

Abstract Individual-level interventions are inadequate to address complex societal problems. Meaningful solutions require system-level policies that alter the incentives that govern behavior. We argue that individual-level interventions can help improve both the feasibility and effectiveness of system-level interventions, especially when designed as an integrated policy package.
Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis
Authors: Zelma C. Chiesa Fuxench, Joy Wan, Sonia Wang, Maha N. Syed, Daniel B. Shin, Katrina Abuabara, Joel M. Gelfand
Journal: JAMA Dermatology (2023)

Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately.
Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors
Authors: Hari S. Iyer, Nur Zeinomar, Angela R. Omilian, Marley Perlstein, Melissa B. Davis, Coral O. Omene, Karen Pawlish, Kitaw Demissie, Chi-Chen Hong, Song Yao, Christine B. Ambrosone, Elisa V. Bandera, Bo Qin
Journal: JAMA Network Open (2023)

Racial disparities in breast cancer (BC) survival arise from multilevel causes, which may exert influence at different stages of BC progression. Clarifying the importance of genetic and social factors could help prioritize interventions.
Reporting and Representation of Participant Race and Ethnicity in National Institutes of Health–Funded Pediatric Clinical Trials
Authors: Lois K. Lee, Claire Narang, Chris A. Rees, Ravi R. Thiagarajan, Patrice Melvin, Valerie Ward, Florence T. Bourgeois
Journal: JAMA Network Open (2023)

Importance Enrolling racially and ethnically diverse pediatric research participants is critical to ensuring equitable access to health advances and generalizability of research findings. Objectives To examine the reporting of race and ethnicity for National Institutes of Health (NIH)–funded pediatric clinical trials and to assess the representation of pediatric participants from different racial and ethnic groups compared with distributions in the US population. Design, Setting, and Participants This cross-sectional study included NIH-funded pediatric (ages 0-17 years) trials with grant funding completed between January 1, 2017, and December 31, 2019, and trial results reported as of June 30, 2022. Exposures National Institutes of Health policies and guidance statements on the reporting of race and ethnicity of participants in NIH-funded clinical trials. Main Outcomes and Measures The main outcome was reporting of participant race and ethnicity for NIH-funded pediatric clinical trials in publications and ClinicalTrials.gov. Results There were 363 NIH-funded pediatric trials included in the analysis. Reporting of race and ethnicity data was similar in publications and ClinicalTrials.gov, with 90.3% (167 of 185) of publications and 93.9% (77 of 82) of ClinicalTrial.gov reports providing data on race and/or ethnicity. Among the 160 publications reporting race, there were 43 different race classifications, with only 3 publications (1.9%) using the NIH-required categories. By contrast, in ClinicalTrials.gov, 61 reports (79.2%) provided participant race and ethnicity using the NIH-specified categories ( P &amp;amp;lt; .001). There was racially and ethnically diverse enrollment of pediatric participants, with overrepresentation of racial and ethnic minority groups compared with the US population. Conclusions and Relevance This cross-sectional study of NIH-funded pediatric clinical trials found high rates of reporting of participant race and ethnicity, with diverse representation of trial participants. These findings suggest that the NIH is meeting its directive of ensuring diverse participant enrollment in the research it supports.
CRISPR-Cas9 Editing of the <i>HBG1</i> and <i>HBG2</i> Promoters to Treat Sickle Cell Disease
Authors: Akshay Sharma, Jaap-Jan Boelens, Maria Cancio, Jane S. Hankins, Prafulla Bhad, Marjohn Azizy, Andrew Lewandowski, Xiaojun Zhao, Shripad Chitnis, Radhika Peddinti, Yan Zheng, Neena Kapoor, Fabio Ciceri, Timothy Maclachlan, Yi Yang, Yi Liu, Jianping Yuan, Ulrike Naumann, Vionnie W.C. Yu, Susan C. Stevenson, Serena De Vita, James L. LaBelle
Journal: New England Journal of Medicine (2023)

Sickle cell disease is caused by a defect in the β-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease. OTQ923, a clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9–edited CD34+ hematopoietic stem- and progenitor-cell (HSPC) product, has a targeted disruption of the HBG1 and HBG2 (γ-globin) gene promoters that increases fetal hemoglobin expression in red-cell progeny. We performed a tiling CRISPR-Cas9 screen of the HBG1 and HBG2 promoters by electroporating CD34+ cells obtained from healthy donors with Cas9 complexed with one of 72 guide RNAs, and we assessed the fraction of fetal hemoglobin–immunostaining erythroblasts (F cells) in erythroid-differentiated progeny. The gRNA resulting in the highest level of F cells (gRNA-68) was selected for clinical development. We enrolled participants with severe sickle cell disease in a multicenter, phase 1–2 clinical study to assess the safety and adverse-effect profile of OTQ923. In preclinical experiments, CD34+ HSPCs (obtained from healthy donors and persons with sickle cell disease) edited with CRISPR-Cas9 and gRNA-68 had sustained on-target editing with no off-target mutations and produced high levels of fetal hemoglobin after in vitro differentiation or xenotransplantation into immunodeficient mice. In the study, three participants received autologous OTQ923 after myeloablative conditioning and were followed for 6 to 18 months. At the end of the follow-up period, all the participants had engraftment and stable induction of fetal hemoglobin (fetal hemoglobin as a percentage of total hemoglobin, 19.0 to 26.8%), with fetal hemoglobin broadly distributed in red cells (F cells as a percentage of red cells, 69.7 to 87.8%). Manifestations of sickle cell disease decreased during the follow-up period. CRISPR-Cas9 disruption of the HBG1 and HBG2 gene promoters was an effective strategy for induction of fetal hemoglobin. Infusion of autologous OTQ923 into three participants with severe sickle cell disease resulted in sustained induction of red-cell fetal hemoglobin and clinical improvement in disease severity. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT04443907.)
Don't throw the individual perspective out while waiting for systemic change
Authors: Elizabeth S. Collier, Kathryn L. Harris, Michael Jecks, Marcus Bendtsen
Journal: Behavioral and Brain Sciences (2023)

Abstract Although it is clear that i-frame approaches cannot stand alone, the impact of s-frame changes can plateau. Combinations of these approaches may best reflect what we know about behavior and how to support behavioral change. Interactions between i-frame and s-frame thinking are explored here using two examples: alcohol consumption and meat consumption.
Mind the Gap — Timing of Cleft Palate Repair
Authors: Raymond Tse, Oksana Jackson
Journal: New England Journal of Medicine (2023)

Orofacial clefts are the most common congenital facial anomaly. Fusion of the primary palate at 4 to 6 weeks of gestation facilitates the formation of the lip, nose, alveolus, and anterior hard palate. Fusion of the secondary palate at 6 to 12 weeks of gestation facilitates the formation of the posterior hard palate and the soft palate. The failure of fusion results in a gap that we call a "cleft." Variation in the extent of the cleft results in patients with a wide spectrum of clinical presentations, which may or may not be associated with a syndrome. The trial by . . .
PICH Activates Cyclin A1 Transcription to Drive S-Phase Progression and Chemoresistance in Gastric Cancer
Authors: Huili Ye, Wengui Shi, Jing Yang, Long Wang, Xiangyan Jiang, Huiming Zhao, Long Qin, Junjie Qin, Lianshun Li, Weiwen Cai, Junhong Guan, Hanteng Yang, Huinian Zhou, Zeyuan Yu, Hui Sun, Zuoyi Jiao
Journal: Cancer Research (2023)

Abstract The chemotherapeutic agent 5-fluorouracil (5-FU) remains the backbone of postoperative adjuvant treatment for gastric cancer. However, fewer than half of patients with gastric cancer benefit from 5-FU–based chemotherapies owing to chemoresistance and limited clinical biomarkers. Here, we identified the SNF2 protein Polo-like kinase 1-interacting checkpoint helicase (PICH) as a predictor of 5-FU chemosensitivity and characterized a transcriptional function of PICH distinct from its role in chromosome separation. PICH formed a transcriptional complex with RNA polymerase II (Pol II) and ATF4 at the CCNA1 promoter in an ATPase-dependent manner. Binding of the PICH complex promoted cyclin A1 transcription and accelerated S-phase progression. Overexpressed PICH impaired 5-FU chemosensitivity in human organoids and patient-derived xenografts. Furthermore, elevated PICH expression was negatively correlated with survival in postoperative patients receiving 5-FU chemotherapy. Together, these findings reveal an ATPase-dependent transcriptional function of PICH that promotes cyclin A1 transcription to drive 5-FU chemoresistance, providing a potential predictive biomarker of 5-FU chemosensitivity for postoperative patients with gastric cancer and prompting further investigation into the transcriptional activity of PICH. Significance: PICH binds Pol II and ATF4 in an ATPase-dependent manner to form a transcriptional complex that promotes cyclin A1 expression, accelerates S-phase progression, and impairs 5-FU chemosensitivity in gastric cancer.
Limitations of the PREHAB Randomized Clinical Trial—Reply
Authors: Charlotte J. L. Molenaar, Francesco Carli, Gerrit Dirk Slooter
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Age‐adjusted D‐dimer, clinical pre‐test probability‐adjusted D‐dimer, and whole leg ultrasound in ruling out suspected proximal and calf deep venous thrombosis
Authors: Michelangelo Sartori, Laura Borgese, Elisabetta Favaretto, Elisa Lasala, Roberta Bortolotti, Benilde Cosmi
Journal: American Journal of Hematology (2023)

D-dimer (DD) and ultrasonography (US) are part of the diagnostic workup for lower-extremity deep vein thrombosis (DVT). Recent studies have shown that adjusting DD level cut-offs by age or clinical pre-test probability (PTP) decreases the use of US. We compared diagnostic accuracy of PTP-adjusted DD and age-adjusted DD in 3883 patients (F: 61.1%; age: 65.3 ± 16.8 y) referred to our unit for clinically suspected DVT. All patients underwent clinical evaluation, DD, and US. Proximal DVT was detected in 477 (12.4%) patients, and distal DVT was isolated in 342 (8.9%) patients. In the remaining 3064 patients there were 23 venous thromboembolic events (0.75%, 95% CI: 0.50-1.12) during the 3-month follow-up. The specificities of DD, age-adjusted DD, and PTP-adjusted DD in patients without high PTP levels were 47% (95% CI: 45-49), 61% (95% CI: 59-62), and 67% (95% CI: 65-68), respectively. The negative predictive value (NPV) was 96% (95% CI: 95-97) for all diagnostic strategies. When only proximal DVTs were considered, the NPV increased to 99% (95% CI: 98-99). US was avoided in 37% (95% CI: 36-38) of patients with a fixed cut-off DD, 48% (95% CI: 47-50) with age-adjusted DD, and 52% (95% CI: 51-54) with PTP-adjusted DD. The failure rate for all DVTs of DD, age-adjusted DD, and PTP-adjusted DD was 2.0% (95% CI: 1.6-2.5), 2.7% (95% CI: 2.2-3.2), and 2.5% (95% CI: 2.1-3.0), respectively. Compared with the standard DD cut-off, both age-adjusted and PTP-adjusted DD reduced the proportion of patients who required US at the cost of a small increase in failure rate.
Expectations, opportunities, and awareness: A case for combining i- and s-frame interventions
Authors: Ben R. Newell, Samuel Vigouroux, Harry Greenwell
Journal: Behavioral and Brain Sciences (2023)

Abstract We argue that: (1) disappointment in the effectiveness of i-frame interventions depends on realistic expectations about how they could work; (2) opportunities for system reform are rare, and i-frame interventions can lay important groundwork; (3) Chater &amp; Loewenstein's evidence that i-frame interventions detract from s-frame approaches is limited; and (4) nonetheless, behavioural scientists should consider what more they can contribute to systemic reforms.
Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia
Authors: Samuel J. Dienel, Kevin F. Dowling, Zackery Barile, H. Holly Bazmi, Amy Liu, Julia C. Vespoli, Kenneth N. Fish, David A. Lewis
Journal: JAMA Psychiatry (2023)

Individuals with schizophrenia (SZ) exhibit pronounced deficits in somatostatin (SST) messenger RNA (mRNA) levels in the dorsolateral prefrontal cortex (DLPFC). Molecularly distinct subtypes of SST neurons, located in the superficial and deep zones of the DLPFC, are thought to contribute to different functional processes of this region; understanding the specificity of SST alterations in SZ across these zones could inform the functional consequences of those alterations, including cognitive impairments characteristic of SZ.